tbuckley/cabot-search huggingface dataset:
Abstract 13045: Increased Recognition of Transthyretin Amyloid Cardiomyopathy as a Cause of Heart Failure in Women
Authors: Mark Prasad, Morris Kim, Pranav Chandrashekar, Yuanzi Zhao, Katherine Fischer, Babak Nazer, Ahmad Masri
Journal: Circulation (2022)

Introduction: Recognition of transthyretin amyloid cardiomyopathy (ATTR-CM) as a cause of heart failure has increased over the past decade. ATTR-CM, particularly wild type (wtATTR-CM), is considered to mainly affect men. Tafamidis was approved by the FDA for the treatment of ATTR-CM based on the results of the ATTR-ACT trial, which only included 13 women with wtATTR-CM (out of 335). We investigated the proportion of women diagnosed with ATTR-CM over time and compared their presenting characteristics to men. Hypothesis: Improved recognition of ATTR-CM has uncovered a higher prevalence of ATTR-CM in women compared to historical estimates. Methods: We compared the presenting characteristics of women to men diagnosed with ATTR-CM. We also compared the proportions of women with ATTR-CM diagnosed before 2019 with those diagnosed 2019-2022. Subgroup analysis of wtATTR-CM patients was performed as well. Results: Over the study period, 140 consecutive patients (81% wild type, 11.4% women) with ATTR-CM were included. The rate of diagnosis of hereditary ATTR-CM in women did not change from pre 2019 (4/69 or 6%) to 2019-2022 (5/71 or 7%). However, for wtATTR-CM, there were 0 women and 51 men diagnosed prior to 2019 as compared to 7 women (11%) and 62 men from 2019-2022. There were several differences in the presenting characteristics between men and women in the combined ATTR-CM group (Table). However, in the wtATTR-CM group, the only significant differences were higher left ventricular ejection fraction and smaller systolic and diastolic diameters in women (Table). Conclusions: There has been a rapid increase in the rate of diagnosis of wtATTR-CM in women. Ongoing education and a changing diagnostic landscape will redefine wtATTR-CM epidemiology.
Abstract 14223: Lifetime Smoking Behaviors, Frequency of Worship and Systolic Blood Pressure in the Metabolic Syndrome Outcome (MetSO) Cohort Study
Authors: Judite Blanc, Bruno Oliveira, April Rogers, Ana Sanchez Alfonso, Azizi A Seixas, Girardin Jean-Louis
Journal: Circulation (2022)

Introduction: Research has shown faith-based intervention can influence a net reduction of 5.8 millimeters of mercury in systolic blood pressure 1 . This study examined the relationships between lifetime smoking behaviors and systolic blood pressure (BP) in a diverse sample of Blacks residing in New York City and whether this relationship is moderated by frequency of visit to place of worship. Method: The present study utilized data from the MetSO study, an NIH-funded cohort study of blacks with metabolic syndrome (MetS). A total of 1035 were screened for MetS in the MetSO registry. The average age of the sample was 62±14 years (range: 20-97); 71% were female, and all were of the black race/ethnicity. Seventy-one percent reported finishing high school, and 43% reported annual income &lt;10K. Patients were diagnosed with MetS using standard criteria articulated in the joint interim statement for harmonizing the MetS. Data was gathered on demographics, health behaviors and religious practices. Participants were asked about their smoking habits and alcohol consumption, as well as their religious practices. Correlation matrix and multilinear regression analysis were conducted to explore associations between smoking behaviors and blood pressure level. Interaction effects between smoking behaviors and potential moderators (frequency of visits to place of worship) were conducted to examine which category was at greater risk of higher systolic blood pressure. Results: Surprisingly, lifetime smoking habits were positively correlated with frequency of visit to place of worship (r =.41; p=.000) and emerged as the strongest independent predictor of systolic BP [β =.084(SE=1.068); p&lt; 0.001], after adjustment for age, employment and daily alcohol consumption. The association between lifetime smoking habits and systolic BP was moderated by the frequency of visits to place of worship [B(SE)=.098 (.150); p&lt; 0.001]. Conclusions: Results of our study suggest that frequency of visit to place of worship is linked with lifetime smoking habits, which may have significant impact on systolic blood pressure among diverse older Blacks.
Abstract 14894: Mst1 Mediates Doxorubicin-Induced Cardiomyopathy by Sirt3 Downregulation
Authors: Leonardo Schirone, Daniele Vecchio, Maurizio Forte, Sonia Schiavon, Luca D'Ambrosio, Sebastiano Sciarretta
Journal: Circulation (2022)

INTRODUCTION: Heart failure is a major side effect of doxorubicin (DOX) treatment in patients with cancer. However, the mechanisms underlying the development of DOX-induced cardiomyopathy (DCM) need to be addressed. Here, we demonstrate that the serine/threonine kinase MST1, a major component of the Hippo pathway, contributes to the development of DOX-induced myocardial injury. HYPOTHESIS: The inhibition of MST1 protects from DCM by preserving SIRT3 expression METHODS: C57BL/6J WT mice and mice with cardiomyocyte-specific dominant-negative MST1 (kinase-dead, DN-MST1) overexpression received 3 weekly injections of DOX, reaching a final cumulative dose of 18 mg/kg. Echocardiographic, histological and biochemical analyses were performed 6 weeks after the first administration of DOX. RESULTS: MST1 signaling was significantly activated in cardiomyocytes in response to DOX treatment in vitro and in vivo. Wild-type (WT) mice treated with DOX had reduced fractional shortening (46,1±1,8 vs. 31,1±1,1, n=7-11, p&lt;0.0001) and TEM mitochondrial abnormalities (3,7±0,9 vs. 10,2±1,5, n=12, p&lt;0.0001). However, systolic dysfunction was abolished in mice with CM-specific overexpression of DN-MST1 (31,1±1,1 vs. 46,3±1,1, n=11, p&gt;0.0001) or treated with the MST1 inhibitor ‘XMU-MP-1’ (37,5±1,8 vs. 46,6±1,9, n=8, p&lt;0.01), indicating that MST1 inhibition attenuates DOX-induced cardiac dysfunction. DOX treatment also led to a significant downregulation of cardiac levels of SIRT3 (1±0,1 vs. 0,6±0,1, p&lt;0.05), a deacetylase involved in mitochondrial protection, in WT mice, which was rescued by MST1 inhibition (0,6±0,1 vs. 1,3±0,04, p&lt;0.001). Pharmacological inhibition of SIRT3 blunted the protective effects of MST1 inhibition (44,5±1,6 vs. 32,5±2,3, n=4, p&lt;0.01), indicating that SIRT3 downregulation mediates the cytotoxic effects of MST1 activation in response to DOX treatment. Finally, we found a significant upregulation of MST1 levels in human myocardial tissue of cancer patients treated with DOX (1,5±0,23 vs. 2,4±0,12, N=81-123 cells from 3 different patients, p&lt;0.001). CONCLUSION: MST1 contributes to DOX-induced cardiomyopathy by promoting mitochondrial damage through SIRT3 downregulation in cardiomyocytes.
Abstract 13776: Alpha 1-Acid Glycoprotein is Involved With Neutrophil Nets in COVID-19
Authors: Fabiola Mestriner, Lígia C Campos, Daniely Franco Francisco, Ariel Couto, Thais F Fraga-Silva, Vinicius Flora Dugaich, Carolina D Avila Mesquita, Elizabete R Milani, Ronaldo Martins, Carlos Corsi, Jessyca Michelon, Jociany Vasconcelos, Tauana F Vasconcelos, Bruno Petroski, Daniel M Couto, Maria CecÃlia Jordani, Rafael M da Costa, Mayra G Menengueti, Paulo Roberto B Evora, Rita C Tostes, Vania L Bonato, Maria A Martins, Maurício S Ribeiro, Christiane Becari
Journal: Circulation (2022)

Introduction: Orosomucoid also named Alpha-1 Acid Glycoprotein(AGP) is a major acute-phase protein and is increased in response to systemic injury and inflammation. AGP has been described as an inhibitor of neutrophil migration on sepsis, particularly its immunomodulation effects. The AGP biological functions are not understood in Coronavirus disease 2019 (COVID-19). Hypothesis: We hypothesize that plasmatic AGP is upregulated in severe Covid-19 patients and is involved in the regulation of netosis. Therefore, we sought to investigate the role of AGP in plasmatic from COVID-19 severe infection patients and neutrophils infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SarsCov-2). Methods: Epidemiological data and AGP, interleukin-6 (IL-6), C-reactive protein (PCR), lactate, and other laboratorial parameters were measured in blood samples from 52 subjects hospitalized in the ICU with clinically SarsCov-2 infection confirmed by RT-PCR. To evaluate the role of AGP in netosis in neutrophils, blood samples from health patients (n=13) were collected, and neutrophils were separated and infected with Sars-Cov-2 (Moi=1). Those neutrophils were treated with AGP (10μg/ml) or vehicle for 18 hours and netosis was analyzed by flow cytometry (n=10) and immunofluorescence (IF; n=10). Early and late netosis, respectively, were characterized by negative or positive FVS and positive Sytox. The neutrophil extracellular traps (NETs) were investigated by myeloperoxidase (MPO), neutrophil elastase (NE), and DAPI by IF and quantified Netquant/Matlab software. This study was approved by Ethics Committee -CAAE: 30816620.0.0000.5440. Results: AGP increased in severe Covid-19 patients (p&lt;0.05). A positive correlation between AGP with IL-6 and C-reactive protein (respectively, p=0.005, p=0.002) and a negative correlation between AGP and lactate (p=0.004) were found it. Together, AGP treatment downregulated early (35,7%) and late (43,5%) netosis in neutrophils infected with SarsCov-2. Confocal analysis by MPO, NE e DAPI showed NETs released by neutrophils infected with Sar-Cov-2 decreased when neutrophils were treated with AGP (p&lt;0.05). Conclusions: Our data showed increased AGP in COVID-19 infection and contributed to netosis regulation.
Abstract 13182: Inhibition of Microrna-466 and Microrna-200 Accelerates Wound Healing by Decreasing Endothelial Cell Permeability
Authors: Hainan Li, Marisa Kujawa, Megan O'Meara, Liping Xu, Jie-Mei Wang
Journal: Circulation (2022)

Introduction: Endothelial cell (EC) permeability is essential to vascular homeostasis in diabetes. MicroRNAs (miRs) are critical gene regulators whose roles in the EC permeability have yet to be elucidated. It remains unclear whether miR-200 and miR-466 regulate EC permeability. We hypothesized that the inhibition of miR-466 and miR-200 can restore vascular integrity and accelerate wound healing via targeting Claudin-5. Methods and Results: Human dermal microvascular ECs from healthy subjects and type 2 diabetic patients at passages 5-7 were cultured in vitro. The EC permeability was significantly increased by high glucose (25mM)or silencing Claudin-5 as measured by FITC-Dextran Transwell assay (n = 5, p&lt;0.05). Claudin-5 protein levels were significantly reduced in diabetic ECs and healthy ECs exposed to high glucose. The reduction of Claudin-5 protein was restored by the inhibition of miR-466 (Western Blot, n = 5, p&lt;0.05), though both miR-200 and miR-466 are directly bound with the 3’ UTR of Claudin-5 mRNA (luciferase 3’UTR reporter assay). Furthermore, silencing Claudin-5 diminished the protection of miR-200/miR-466 inhibition on EC permeability damaged by high glucose (n = 5, p&lt;0.05). In the in vivo study, the topical application of miR-200 and miR-466 inhibitors showed enhanced efficacy in accelerating the closure of a 7-mm full-thickness excisional wound in a type 2 diabetic (db/db) mouse model, with concomitant robust wound capillary formation (CD31 immunochemistry), compared with the topical application of miR-200 inhibitor alone (n = 5, p&lt;0.05). Claudin-5 levels were increased in the wounds receiving miR-466 inhibitor alone or both miR-200 and miR-466 inhibitors (n = 5, p&lt;0.05). Conclusions: Our study demonstrated the potentially effective approach of miR-200/miR-466 cocktail inhibition to restore vascular integrity and tissue repair in hyperglycemia. This may provide a novel therapeutic strategy targeting miRs for the treatment of wound healing in diabetes.
Abstract 13910: Racial/Ethnic Outcomes Following Percutaneous Coronary Intervention
Authors: Daniel R Wang, Joshua Li, Rushi Parikh, Boback Ziaeian, Nicholas J Jackson, Jeffrey J Hsu
Journal: Circulation (2022)

Introduction: Asian-American/Pacific Islanders (AAPIs) and Hispanics are two of the most rapidly growing minorities, but both are poorly represented in the cardiovascular literature. In light of national quality improvement efforts to ensure adherence to cardiovascular therapy guidelines, this study examines guideline adherence and outcomes in AAPIs and Hispanics compared to non-Hispanic Whites (NHW) in a quaternary care center after percutaneous coronary intervention (PCI). Methods: 1,896 AAPI, Hispanics, and NHW adults from February 28, 2012 to December 30, 2020 who underwent emergent or elective PCI were included. The primary endpoint was the prescription of post-PCI guideline-directed medical therapy including aspirin, statins, P2Y12 receptor blockers, and cardiopulmonary rehabilitation. Secondary endpoints included comorbidity burden, post-PCI morbidity and mortality, and prior PCI. Analyses were adjusted for age, sex, and insurance type. Results: Hispanics had the lowest median age and the highest rates of government insurance. Hispanics had lower odds of either ACE inhibitor or ARB prescription versus NHW (OR = 0.75, p = 0.03). Odds of ticagrelor prescriptions were lower for both Hispanics (OR = 0.56, p = 0.01) and AAPIs (OR = 0.62, p = 0.02) versus NHW. However, odds of clopidogrel prescriptions were higher for Hispanics than NHW (OR = 1.57, p = 0.01), while AAPIs trended towards the same (OR = 1.42, p = 0.05). No differences were found for statin or cardiopulmonary rehabilitation prescriptions. AAPIs and Hispanics had significantly higher risks of diabetes (OR = 2.28 and 1.8 respectively, p &lt; 0.01) and of being on dialysis (OR = 2.25 and 2.52 respectively, p &lt; 0.01) than NHW. AAPIs also had higher odds of hypertension than NHW (OR = 1.51, p = 0.01). Hispanics had significantly higher risk of post-PCI mortality versus NHW (OR = 2.12, p &lt; 0.01). Conclusions: AAPIs and Hispanics had lower odds of ticagrelor prescription than NHW, and Hispanics had higher odds of clopidogrel prescription. Hispanics also had higher odds of mortality post-PCI. Further, AAPIs and Hispanics had higher comorbidity burdens. This study suggests that despite quality improvement efforts, work remains to be done to narrow health disparities.
Abstract 14128: Impact of Sarcoidosis in Patients Undergoing Aortic Valve Replacement: Insight From National Readmission Database 2016-2019
Authors: Kunal Patel, Harshvardhan Zala, Monil Majmundar, Avleen kaur, Vyoma Patel, Rajkumar P Doshi, Christian Toquica Gahona, Abi Watts, Heminder Singh, Keval V Patel, MD, Sourbha Dani, Ankur Kalra
Journal: Circulation (2022)

Introduction: Limited data exist on the in-hospital and readmission outcomes in sarcoidosis patients after surgical or transcatheter aortic valve replacement (SAVR/TAVR). Hypothesis: Sarcoidosis can lead to cardiac conduction abnormalities and cardiomyopathy which can lead to poor outcomes after aortic valve intervention (AVI). We hypothesize that SAVR/TAVR in sarcoidosis patients has the worst outcomes. Methods: The NRD was queried for all sarcoidosis patients who underwent SAVR/TAVR from 2016-2019. Our outcomes of interest were in-hospital mortality, in-hospital complications, and 30-day readmissions for heart failure and pacemaker implantation. Clinical outcomes were modeled using logistic regression for binary outcomes and linear regression for continuous outcomes. Results: We identified a total of 507,441 SAVR/TAVR hospitalizations of which 1429 were of sarcoidosis patients. Patients with sarcoidosis were younger (mean age 70.1 years vs 72.4 years) and had more women (48.3% vs 38.2%, p&lt;0.001). In-hospital mortality occurred in 35 (2.5%) patients with sarcoidosis and in 13,367 (2.6%) patients without sarcoidosis. After SAVR/TAVR, the risk of in-hospital mortality in sarcoidosis patients was similar to patients without sarcoidosis (OR: 0.86, 95% CI 0.50 - 1.48, p = 0.58). Risks of stroke, cardiogenic shock, pacemaker implantation, paravalvular leak, AKI requiring dialysis, hemorrhage requiring transfusion, cardiorespiratory complications, need for cardiothoracic procedures, 30-day heart failure and pacemaker implantation readmissions were also similar in patients with and without sarcoidosis. Conclusions: Sarcoidosis is not associated with an increased risk of in-hospital mortality, in-hospital complications and 30-day readmissions for heart failure and pacemaker implantation. Thus, AVI is possibly not futile in sarcoidosis patients and future studies are necessary to understand the benefits of AVI in these patients.
Abstract 13406: Atrial Fibrillation and Atrial Flutter as Predictors of Cardiovascular Outcomes in Patients Hospitalized With Covid-19 Infection
Authors: Beatriz Rivera Rodriguez, Laura Aponte Becerra, Crystal Yan, LAURA MCDERMOTT, Ramon Romano Peralta, Neal Olarte, Sharon Andrade-Bucknor
Journal: Circulation (2022)

Introduction: Patients with atrial structural changes have a higher risk of developing atrial arrhythmias, such as atrial fibrillation (AF) and flutter (AFL), particularly during pro-inflammatory states such as a COVID-19 infection. Amongst these patients, AF/AFL have been found to be markers of disease severity. Our aim was to evaluate AF/AFL as predictors of cardiovascular outcomes, and their synergistic relationship with atrial dilatation, in patients with COVID-19. Methods: We conducted a two-center retrospective study in patients hospitalized with COVID-19 from 2020 to 2021. Atrial enlargement was defined by 2D-guided linear measurement by echocardiography. The primary outcome of interest was to determine the association of MACE, defined as myocardial infarction, non-fatal stroke, cardiac arrest, and/or death, in patients who developed AF/AFL. The secondary outcome was to explore the synergistic risk of atrial enlargement and AF/AFL on MACE. Statistical analyses were performed using SAS 9.4. Results: From 488 patients, 68 (14%) developed AF/AFL. These patients were older (74±11 vs. 64±15 years), had higher rates of hypertension (79% vs. 64%), coronary artery disease (29% vs. 12%), and heart failure (28% vs 10%). There was a significant unadjusted effect of right atrial enlargement (OR 2.12, CI 1.15-3.91) and AF/AFL (OR 1.90, CI 1.14-3.19) on MACE, whereas the effect was not sustained for left atrial enlargement. Multivariable adjusted models showed that AF/AFL and right atrial enlargement had no longer a significant effect on MACE, and only age remained an independent significant predictor (OR 1.27, CI 1.09-1.47). Moreover, there was no joint effect of AF/AFL and right atrial enlargement on MACE when their interaction was accounted for. Conclusion: AF and AFL were not associated with a higher risk of MACE, nor was atrial enlargement shown to modify the relationship between AF/AFL and MACE in patients who were hospitalized with COVID-19. Age remains to be a predictor of poor outcomes. Studies with a larger sample size would be needed to determine if there’s a significant relationship.
Abstract 13056: Evaluation of Stable Angina by Coronary Computed Tomographic Angiography versus Standard of Care: A Systematic Review and Meta-Analysis
Authors: Anirudh Palicherla, Mahmoud Ismayl, Abhishek Thandra, Kashif Shaikh
Journal: Circulation (2022)

Introduction: There has been growing evidence comparing Coronary Computed Tomography Angiography (CCTA) versus the standard of care(SOC) in patients with suspected stable coronary artery disease (CAD). We aimed to perform a systematic review and meta-analysis to compare CCTA versus SOC in patients with stable CAD. Methods: We searched multiple databases for randomized controlled trials (RCTs) comparing CCTA with SOC with various functional testing approaches for the evaluation of stable CAD. We used a random-effects model to calculate risk ratios (RRs) with 95% confidence intervals (CIs). Outcomes included all-cause mortality, myocardial infarction (MI), hospitalization for unstable angina (UA), invasive angiography, revascularization, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). Results: We identified 6 RCTs with a total of 19,881 patients with stable CAD, of which 9,995 underwent CCTA and 9,886 underwent UC. There were no significant differences between CCTA and SOC in terms of all-cause mortality (RR: 0.91; 95% CI: 0.70-1.19; p=0.64), MI (RR: 0.78; 95% CI: 0.58-1.05; p=0.70), hospitalizations for UA (RR: 1.20; 95% CI: 0.95-1.51;p=0.64), invasive angiography (RR: 0.11; 95% CI: 0.32-1.61; p&lt;0.00001), revascularization (RR:1.25; 95% CI: 0.83-1.89; p&lt;0.00001), PCI (RR: 1.20; 95% CI: 0.78-1.85; p&lt;0.00001), and CABG rates (RR: 0.89; 95% CI: 0.530-1.49; p=0.0003). Conclusions: In patients with stable CAD, CCTA is associated with similar outcomes compared to the usual standard of care. Given its non-invasive nature and capability to evaluate atherosclerotic plaque burden, CCTA may be preferred as an initial strategy for the evaluation of patients with stable CAD.
Abstract 13826: Atrial Fibrillation Catheter Ablation in Patients With Inflammatory Bowel Disease
Authors: Ikram-Ul Haq, Anan Abu Rmilah, Hossam Alzu'bi, Abhishek Deshmukh, Christopher V Desimone
Journal: Circulation (2022)

Introduction: Patients with a history of inflammatory bowel disease (IBD) are at a higher risk of atrial fibrillation (AF). There is a lack of evidence supporting catheter ablation in this group and predictors of procedural outcomes are unknown. Hypothesis: We assessed the hypothesis that patients with a history of IBD have worse procedural outcomes with more peri-procedural complications, especially in those whose disease is less well controlled. Methods: A single-center 1:1 propensity matched study of patients with no history of IBD and patients with IBD who underwent primary AF catheter ablation from January 2010 to December 2021 was conducted. The primary outcome was procedural efficacy defined by clinical AF recurrence and repeat catheter ablation. The secondary outcome was an assessment of safety looking at eight peri-procedural events. Univariate and multivariate binary logistic regression analysis was conducted to determine predictors of AF recurrence. Results: Our cohort was comprised of 94 patients, 47 patients with a history of IBD (mean age 64.7 ± 6.4 years) and 47 patients with no history of IBD (66.7 ± 7.1 years). Both groups had similar echocardiographic, baseline, and arrhythmia characteristics. All patients underwent pulmonary vein isolation and procedural endpoints were ascertained in all patients. At one-year post-ablation, the study group was statistically more likely to develop AF recurrence (OR 2.38, 95% CI 1.09 - 4.86, p=0.03) but were equally likely to undergo repeat catheter ablation (OR 2.56, 95% CI 0.62 - 10.6, p=0.19). Procedural safety was statistically similar in both groups. Four patients in the study group and three patients in the control group developed subcutaneous hematomas at the site of instrumentation (p=0.70). Multivariate analysis found pre-procedural c-reactive protein (CRP) (OR 1.04, 95% CI 1.00 - 1.12) and AF diagnosis to ablation time (OR 1.15, 95% CI 1.03 - 1.24) were independent predictors of post-procedure AF recurrence. Conclusions: Our study suggests patients with IBD are at a higher risk of developing AF recurrence after catheter ablation. Multivariate analysis showed CRP and AF diagnosis to time to ablation were both independent risk factors.